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Abstract Background Autoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis. Incomplete biochemical response is the most important risk factor for liver transplantation or liver-related mortality. First-line treatment consists of a combination of azathioprine and prednisolone. If CR is not reached, tacrolimus (TAC) or mycophenolate mofetil (MMF) can be used as second-line therapy. Both products are registered for the prevention of graft rejection in solid organ transplant recipients. The aim of this study is to compare the effectiveness and safety of TAC and MMF as second-line treatment for AIH. Methods The TAILOR study is a phase IIIB, multicentre, open-label, parallel-group, randomised (1:1) controlled trial performed in large teaching and university hospitals in the Netherlands. We will enrol 86 patients with AIH who have not reached CR after at least 6 months of treatment with first-line therapy. Patients are randomised to TAC (0.07 mg/kg/day initially and adjusted by trough levels) or MMF (max 2000 mg/day), stratified by the presence of cirrhosis at inclusion. The primary endpoint is the difference in the proportion of patients reaching CR after 12 months. Secondary endpoints include the difference in the proportion of patients reaching CR after 6 months, adverse effects, difference in fibrogenesis, quality of life and cost-effectiveness. Discussion This is the first randomised controlled trial comparing two second-line therapies for AIH. Currently, second-line treatment is based on retrospective cohort studies. The rarity of AIH is the main issue in clinical research for alternative treatment options. The results of this trial can be implemented in existing international clinical guidelines. Trial registration ClinicalTrials.gov NCT05221411 . Retrospectively registered on 3 February 2022; EudraCT number 2021–003420-33. Prospectively registered on 16 June 2021.

Izabela Rumienczyk,1 Maria Kulecka,1,2 Jerzy Ostrowski,1,2 Daniel Mar,3 Karol Bomsztyk,3 Stephen W Standage,4,5 Michal Mikula1 1Maria Sklodowska-Curie National Research Institute of Oncology, Department of Genetics, Warsaw, 02-781, Poland; 2Centre for Postgraduate Medical Education, Department of Gastroenterology, Hepatology and Clinical Oncology, Warsaw, 01-813, Poland; 3UW Medicine South Lake Union, University of Washington, Seattle, WA, 98109, USA; 4Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; 5Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USACorrespondence: Michal MikulaMaria Sklodowska-Curie National Research Institute of Oncology, Department of Genetics, Warsaw, 02-781, PolandTel +48225462655Email michal.mikula@pib-nio.plPurpose: During sepsis, an excessive inflammatory immune reaction contributes to multi-organ dysfunction syndrome (MODS), a critical condition associated with high morbidity and mortality; however, the molecular mechanisms driving MODS remain elusive.Methods: We used RNA sequencing to characterize transcriptional changes in the early phase of sepsis, at 6, 12, 24 hour time points in lung, kidney, liver, and heart tissues, in a cecal ligation and puncture (CLP)-induced polymicrobial sepsis murine model.Results: The CLP surgery induced significant changes (adj. p-value< 0.05) in expression of hundreds of transcripts in the four organs tested, with the highest number exceeding 2,000 differentially expressed genes (DEGs) in all organs at 12 hours post-CLP. Over-representation analysis by functional annotations of DEGs to the Reactome database revealed the immune system, hemostasis, lipid metabolism, signal transduction, and extracellular matrix remodeling biological processes as significantly altered in at least two organs, while metabolism of proteins and RNA were revelaed as being liver tissue specific in the early phase of sepsis.Conclusion: RNA sequencing across organs and time-points in the CLP murine model allowed us to study the trajectories of transcriptome changes demonstrating alterations common across multiple organs as well as biological pathways altered in an organ-specific manner. These findings could pave new directions in the research of sepsis-induced MODS and indicate new sepsis treatment strategies.Keywords: sepsis, RNA-seq, reactome, murine model

This paper presents the development of a deformable connection that is used to connect each floor system of the flexible gravity load resisting system (GLRS) with the stiff lateral force resisting system (LFRS) of an earthquake-resistant building. It is shown that the deformable connection acts as a seismic response modification device, which limits the lateral forces transferred from each floor to the LFRS and allows relative motion between the GLRS and LFRS. In addition, the floor accelerations and the LFRS story shears related to the higher-mode responses are reduced. The dispersion of peak responses is also significantly reduced. Numerical simulations of the earthquake response of a 12-story reinforced concrete shear wall example building with deformable connections are used to define an approximate feasible design space for the deformable connection. The responses of the example building model with deformable connections and the example building model with rigid-elastic connections are compared. Two configurations of the deformable connection are studied. In one configuration, a buckling restrained brace is used as the limited-strength load-carrying hysteretic component of the deformable connection, and in the other configuration, a friction device is used. Low damping laminated rubber bearings are used in both configurations to ensure the out-of-plane stability of the LFRS and to provide post-elastic stiffness to the deformable connection. Important experimental results from full-scale tests of the deformable connections are presented and used to calibrate numerical models of the connections. Copyright © 2016 John Wiley & Sons, Ltd.

This paper assessed the extent of the implementation of the Provincial Ordinance 2012-09 or the No Plastic Policy in the Municipality of Balagtas, Bulacan. Since plastic waste is one of the evident issues in the municipality, the study aimed to assess the extent and determine the challenges encountered in the implementation of the No Plastic Policy which was signed in order to address the issues related to plastic wastes. The extent of the implementation of the policy was gathered through survey questionnaires distributed to business sectors and households while semi-structured interviews were conducted among the key implementers to determine the challenges encountered. The findings of the study showed that the extent of the implementation of the No Plastic Policy was somewhat implemented and the challenges encountered include costly and limited alternatives; lack of clarity in the operational guidelines; non-compliance of the residents; and lack of strict implementation efforts. Thus, the findings of the study showed that there is a need to strengthen the existing ordinance in the Municipality of Balagtas, Bulacan. [ABSTRACT FROM AUTHOR]

Seagrasses provide diverse ecosystem services that support communities, yet, they are among the most threatened marine habitats. Efforts to conserve and sustainably manage seagrasses are increasing, particularly amidst the era of climate change, in which they play a critical role. However, these activities often received less attention or were slow in gaining momentum partly due to a lack of societal recognition of seagrasses and their importance. Thus, in this study, we collected community perceptions of seagrass ecosystem services and threats from 391 respondents in Karimunjawa National Park (KNP), a nationally declared protected area in Indonesia. We aim to provide insights on people's recognition of seagrasses from a local scale with strict protection measures. Overall, respondents showed varying perceptions of seagrass ecosystem services, with provisioning services more highly perceived than regulating services. The perceived level of threats was inconclusive, though, reclamation along shorelines received higher rates (leaning toward most damaging) than other threats such as natural disasters and illegal fishing activities. Sociodemographic attributes of respondents were found to influence their perceptions, with occupation as the most pronounced driving factor. The variations observed in seagrass perceptions suggest that there is a need to strengthen and/or enhance seagrass awareness and education campaigns, which is in line with the increasing demand that public perceptions matter for the conservation and sustainable management of seagrass ecosystems. We presented here the use and insights of community perceptions for seagrass blue carbon conservation in KNP, and consequently in Indonesia, where seagrass meadows are considered globally important carbon sinks. [ABSTRACT FROM AUTHOR]

Seagrass meadows provide diverse ecosystem services that directly or indirectly benefit the coastal communities. Despite this, they are among the most threatened coastal ecosystems. Though coastal and marine conservation actions have progressed over the years, seagrasses received less attention compared with other more charismatic ecosystems such as coral reefs and mangroves. Among the influencing factors, the lack of societal recognition of what seagrasses are and their importance underlies the global crisis of seagrass conservation. Thus, in this study, we gathered rural and urban perceptions of seagrass ecosystem services, their threats, and management‐related activities at the unit of barangay or village in the Philippines. Overall, rural respondents displayed higher awareness of seagrass ecosystem services than urban respondents. Socio‐economic status and personal connection or direct experience to these services influenced their perceptions. Local‐level threats were also perceived and recognizing these at the early onset can avoid severe habitat degradation. Though the role of seagrass blue carbon in climate change mitigation was barely discussed in local contexts, the impact of climate change‐induced stressors on seagrass was perceived by the respondents. Thus, local stakeholders, practitioners, and policymakers have the opportunity to design future seagrass‐focused management plans and programs in the era of climate change. [ABSTRACT FROM AUTHOR]